Adipose tissue-derived stem cells rescue Purkinje neurons and alleviate inflammatory responses in Niemann-Pick disease type C mice
Adipose tissue-derived stem cells rescue Purkinje neurons and alleviate inflammatory responses in Niemann-Pick disease type C mice
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DOI：
10.1007/s00441-010-0942-3
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发表时间：
2010-05-01
影响因子：
3.6
通讯作者：
Jin, Hee Kyung
中科院分区：
文献类型：
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作者：
Bae, Jae-sung;Carter, Janet E.;Jin, Hee Kyung
成体干细胞提供了特殊的治疗前景，因为它们可以分离用于自体移植，体外扩增，并分化成各种细胞类型。我们先前报道了骨髓间充质干细胞改善神经退行性疾病动物模型的神经功能缺损。然而，脂肪组织来源的干细胞（ADSC）移植在类似模型中的疗效仍然未知。在此，我们证明，脂肪干细胞，当移植到尼曼-匹克病C型（NP-C）小鼠小脑，引起浦肯野神经元的救援和运动协调的恢复，以及减轻炎症反应，通过免疫组织化学和实时PCR验证使用胶质细胞酸性蛋白（GFAP），F4/80，IL-1 β，IL-6，和TNF-α。最重要的是，ADSC在NP-C疾病模型小鼠中移植后增强具有功能性突触形成的电活性浦肯野神经元。该报告首次证明了ADSC可以拯救NP-C疾病模型小鼠中受损的浦肯野神经元并减轻炎症反应，从而表明ADSC对神经退行性疾病的治疗潜力。
Adult stem cells offer special therapeutic prospects because they can be isolated for autologous transplantation, expanded ex vivo, and differentiated into various cell types. We previously reported that bone marrow-derived mesenchymal stem cells improve neurological deficits in neurodegenerative disease animal models. However, the efficacy of adipose tissue-derived stem cells (ADSCs) transplantation in similar models remains unknown. Herein, we demonstrate that ADSCs, when transplanted into Niemann-Pick disease type C (NP-C) mouse cerebellum, elicit rescue of Purkinje neurons and restoration of motor coordination together with alleviation of inflammatory responses as verified by immunohistochemistry and real-time PCR using glial fibrillary acidic protein (GFAP), F4/80, IL-1 beta, IL-6, and TNF-alpha. Most importantly, ADSCs enhance electrically active Purkinje neurons with functional synaptic formation after transplantation in NP-C disease model mice. This report demonstrates for the first time that ADSCs can rescue imperiled Purkinje neurons and alleviate the inflammatory response in NP-C disease model mice, thereby signifying the therapeutic potential of ADSCs for neurodegenerative diseases.